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Studies in adrenocortical cells have implicated the orphan nuclear receptor SF-1 in the gene regulation of the steroid hydroxylases. We used targeted disruption of the Ftz-F1 gene, which encodes SF-1, to examine its role in intact mice. Despite normal survival in utero, all Ftz-F1 null animals died by postnatal day 8; these animals lacked adrenal glands and(More)
Afferent and efferent connections of the fastigial oculomotor region (FOR) were studied in macaque monkeys by using axonal transport of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). When injected HRP is confined to the FOR, retrogradely labeled cells appear in lobules VIc and VII of the ipsilateral vermis and in group b of the(More)
The cardiac homeobox protein Nkx2-5 is essential in cardiac development, and mutations in Csx (which encodes Nkx2-5) cause various congenital heart diseases. Using the yeast two-hybrid system with Nkx2-5 as the 'bait', we isolated the T-box-containing transcription factor Tbx5; mutations in TBX5 cause heart and limb malformations in Holt-Oram syndrome(More)
As an initial step toward understanding its role in steroidogenesis, we studied the developmental profile of steroidogenic factor-1 (SF-1), a nuclear receptor that regulates the steroid hydroxylases. SF-1 transcripts first appear on embryonic day 9 (E9) in the urogenital ridge, the probable source of steroidogenic cells of both adrenals and gonads. By E11,(More)
The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its(More)
BACKGROUND Ghrelin is a novel growth hormone (GH)-releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF). METHODS AND RESULTS Ligation of the left coronary(More)
Normal male sex differentiation requires that Sertoli cells in the embryonic testes produce müllerian inhibiting substance (MIS), a TGF beta-like hormone that causes müllerian duct regression. In primary Sertoli cells, the orphan nuclear receptor, steroidogenic factor 1 (SF-1), regulates the MIS gene by binding to a conserved upstream regulatory element. In(More)
A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays an essential role in bone accrual and eye development. Here, we show that LRP5 is also required for normal cholesterol and glucose metabolism. The production of mice lacking LRP5 revealed that LRP5 deficiency led to increased plasma cholesterol levels in mice fed a high-fat(More)
Clearance of atorvastatin occurs through hepatic uptake by organic anion transporting polypeptides (OATPs) and subsequent metabolism by cytochrome P450 (CYP) 3A4. To demonstrate the relative importance of OATPs and CYP3A4 in the hepatic elimination of atorvastatin in vivo, a clinical cassette microdose study was performed. A cocktail consisting of a(More)
We have analyzed expression of a gene encoding a brain-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI), which was recently cloned from human brain, in rat forebrain using in situ hybridization. The expression of DNPI mRNA showed a widespread but highly heterogeneous pattern of distribution in the forebrain, where hybridization signals were(More)